Longitudinal alterations of cortical structural-functional coupling in temporal lobe epilepsy.

BACKGROUND AND PURPOSE: To investigate the longitudinal alterations of cortical structural-functional coupling (SF coupling) in patients with temporal lobe epilepsy (TLE) over a 2-year follow-up, thereby exploring the neuropathophysiological mechanisms of TLE. METHODS: Twenty-eight TLE patients and 42 age- and gender-matched healthy controls (HCs) were recruited. We used resting-state functional MRI and diffusion-weighted imaging to estimate and compare SF coupling at the multiscale network level (whole-brain, modular, and regional levels). Then, we analyzed the relationships between the spatial patterns of SF coupling, the principal functional connectivity (FC) gradient, and the functional participation coefficient (PC). Finally, we related regional SF coupling changes between baseline and follow-up to the expression of regional TLE-specific genes. RESULTS: Compared with HCs, TLE patients showed higher baseline SF couplings within the whole-brain, limbic, and default-mode modules. SF couplings within visual and dorsal attention modules were increased at follow-up compared to baseline. In all three groups, the spatial patterns of SF coupling aligned with the principal FC gradient and the functional PC. The longitudinal change in regional SF coupling in TLE patients was significantly positively correlated with the expression of the CUX2 gene. CONCLUSIONS: Aberrant SF coupling was revealed in TLE and related to macroscale cortical hierarchies, functional segregation, and TLE-specific gene expression; these data help increase our understanding of the neuropathophysiological mechanisms underlying TLE.

The alterations of spontaneous neural activities and white matter microstructures in anti-N-methyl-D-aspartate receptor encephalitis: a resting-state fMRI and DTI study.

BACKGROUND AND PURPOSE: Limited studies had jointly excavated the structural and functional changes in cognitive deficit in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients. We aimed to explore these changes in anti-NMDAR patients and their effect on cognitive function. METHODS: Twenty-three patients and 25 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging, diffusion tensor imaging scanning, and neuroethology tests. The significantly differentiated brain regions via the fractional amplitude of low-frequency fluctuation (fALFF) were defined as regions of interest (ROIs). Granger causal, functional connectivity, and tract-based spatial statistical analyses were applied to explore the functional changes in ROIs and assess the structural changes. RESULTS: HCs outperformed patients in Montreal Cognitive Assessment. The fALFF values of right gyrus rectus (RGR) in patients were significantly reduced. The fractional anisotropy (FA) values of WM in the genu of corpus callosum and right superior corona radiata were significantly decreased and positively associated with neuroethology testing scores. The Granger causal connectivity (GCC) from the left inferior parietal lobule to RGR was significantly decreased and positively associated with inherent vigilance. Indicated by the multiple linear regression result, decreased FA value of the right superior corona radiata might be a reliable marker that reflects the cognitive impairment. CONCLUSIONS: Significant changes in spontaneous neural activities, GCC, and WM structures in anti-NMDAR encephalitis were reported. These findings promote the understanding of underlying relationships between cerebral function, structural network alterations, and cognitive dysfunction.

Upregulation of miR­132­3p in cholangiocarcinoma tissues: A study based on RT­qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses.

MicroRNAs (miRNAs/miRs) have been reported to be closely associated with numerous human diseases, including cholangiocarcinoma (CCA). However, the number of miRNAs known to be involved in CCA is limited, and the association between miR­132­3p and CCA remains unknown. In the present study, the clinical role of miR­132­3p and its potential signaling pathways were investigated by multiple approaches. Reverse transcription­quantitative PCR (RT­qPCR), CCA­associated Gene Expression Omnibus (GEO), ArrayExpress and Sequence Read Archive (SRA) miRNA­microarray or miRNA­sequencing data were screened, and meta­analyses were conducted, in order to calculate the receiver operating characteristic (ROC) curve and standardized mean difference (SMD). The predicted target genes of miR­132­3p were obtained from 12 online databases and were combined with the downregulated differentially expressed genes identified in the RNA­sequencing data of CCA. Gene Ontology annotation and pathway analysis were performed in WebGestalt. Protein­protein interaction analyses were conducted in STRING. The Cancer Genome Atlas (TCGA) mRNA expression profiles were used to validate the expression levels of hub genes at the mRNA level. The Human Protein Atlas was used to identify the protein expression levels of hub genes in CCA tissues and non­tumor biliary epithelium. The meta­analyses comprised 10 groups of RT­qPCR data, eight GEO microarray datasets and one TCGA miRNA­sequencing dataset. The SMD of miR­132­3p in CCA was 0.75 (95% CI: 0.25, 1.24), which indicated that miR­132­3p was overexpressed in CCA tissues. This finding was supported by a summary ROC value of 0.80 (95% CI: 0.76, 0.83). The pooled sensitivity and specificity were 0.81 (95% CI: 0.59, 0.93) and 0.71 (95% CI: 0.58, 0.81), respectively. The relative expression level of miR­132­3p in the early stage of CCA (stages I­II) was 6.8754±0.5279, which was markedly lower than that in the advanced stage (stages III­IVB), 7.3034±0.3267 (P=0.003). Consistently, the miR­132­3p level in low­grade CCA (grades G1­G2) was 6.7581±0.5297, whereas it was 7.1191±0.4651 in patients with high­grade CCA (grades G3­G4) (P=0.037). Furthermore, 555 potential target genes of miR­132­3p in CCA were mainly enriched in the 'Focal Adhesion­PI3K­Akt­mTOR­signaling pathway'. In conclusion, upregulation of miR­132­3p may serve a pivotal role in the tumorigenesis and progression of CCA by targeting different pathways. Further in vitro and in vivo studies are required to support the current findings.

Up-regulation of Polo-like Kinase 1 in nasopharyngeal carcinoma tissues: a comprehensive investigation based on RNA-sequencing, gene chips, and in-house tissue arrays.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly invasive malignancy which has unique characteristics when found among individuals from certain ethnic or geographic populations. The role and molecular mechanism of Polo-like kinase 1 (PLK1) in NPC remain yet to be clarified. Hence, the aim of this study is to identify the clinical implications of PLK1 in NPC based on gene chip, tissue microarray, and other silico approaches. METHODS: Relevant data related to PLK1 levels in NPC was screened for by searching in SRA, GEO, ArrayExpress, Oncomine and throughout the existing literature on this topic. The raw data about gene chips were normalized by using an RMA algorithm provided by "Limma" package. Furthermore, the "SVA" package of R software was used to remove the batch effect and data from the same platform were merged into one part. The differential expression levels of PLK1 between NPC and non-NPC tissues were extracted and analyzed with the Student's t-test. Meta-analyses were used to calculate the standard mean difference and sROC. Furthermore, in-house immunohistochemistry was performed with tissue microarrays. Weighted correlation network analysis was used to identify the PLK1-related genes. Several bioinformatic evaluations, including the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interactions, were also performed to assess the PLK1-related pathways. RESULTS: The tissue microarray and gene chips indicated that the PLK1 levels clearly had an up-regulating trend as compared to the non-cancerous controls. These trends were observed in both the single study and the comprehensive meta-analysis. The area under the sROC curve in the NPC tissues was 0.87, with pooled sensitivity and specificity at 0.950 and 0.710, respectively, based on 393 NPC tissues and 83 non-cancerous controls. A total of 144 genes were identified as co-expressed genes of PLK1 in NPC and were mainly enriched in the "cell cycle" pathway. Among the genes related to the cell cycle, CDK1, CCNA2 and CCNB2 were all closely related to PLK1 expression level. CONCLUSIONS: PLK1 may play a potential oncogenic role in the tumorigenesis and development of NPC. Since several PLK1 inhibitors have been developed, it is believed that the PLK1 inhibitors have great therapeutic potential in clinic applications for NPC patients.